The elucidation of covalent protein structure is a valuable tool in every field of biomedical research. This goal, the identification of protein sequence and post-translational modifications, is uniquely facilitated through mass spectrometry. Among mass spectrometers designed to analyze biological samples, quadruple ion trap instruments offer superior sensitivity and high quality fragmentation data, as well as coupling to liquid chromatography. For these reasons, we propose to obtain a LCQ DECA investigators from across campus will make use of this instrument, including a Major Users Group consisting of seven NIH RO1 grantees. The instrument will be used in the following ongoing funded research: Dr. BM Willardson will identity phosphorylation sites, interacting proteins, and transcription factors in his investigations of the roles of the phosducin family of G-protein regulators in modulating signal transduction. Dr. MB Andrus will identify receptor-binding drug candidates from solution-phase natural product-like libraries synthesized in his lab. Dr. TS Elton will identify both DNA and RNA binding proteins that play roles in regulating the expression of the angiotensin receptor. Dr. PB Savage will identify and characterize Lipid A-binding anti-microbial candidates from combinatorial libraries of cationic steroid triamides synthesized in his lab. Dr. DL Simmons will investigate the post-translational modifications of cyclooxygenase 2 and nucleobindin, as part of his research into the roles of these proteins in carcinogenesis and apoptosis. Dr. GF Burton will identify proteins implicated in the function of follicular dendritic cells in AIDS pathogenesis. And Dr. WW Winder will identify post-translational modifications, kinase targets, and transcription factors as part of his ongoing research into the physiology of exercise and type 2 diabetes. The LCQ mass spectrometer enables these investigations which would not be feasible otherwise.